Ionotropic glutamate-like receptor delta2 binds D-serine and glycine - PubMed (original) (raw)
Electrophysiology on WT GluRδ2 and the lurcher mutant GluRδ2Lc receptor. (A) Mean concentration–response curves for
d
-serine (■) and glycine (□) at GluRδ2Lc receptors expressed in Xenopus oocytes. (Inset) The responses (60 s) are normalized to the maximal current response (Δ_I_max) of the indicated ligand. (Calibration bar: 100 nA.) The EC50 values of
d
-serine and glycine are 182 ± 11 μM (n = 9) and 507 ± 40 μM (n = 7), respectively. The maximal current response elicited by glycine was 0.95 ± 0.02 (n = 7) relative to the maximal current response elicited by
d
-serine in the same recording. Error bars (SEM) are small and are contained within the data points. (B) Inhibition of GluRδ2Lc currents in oocytes by application of 1 mM various amino acids, including
d
-serine and glycine. Values are normalized to the inhibition produced by application of 100 μM NASP and are the means ± SEM from 3 to 16 oocytes. (C) Representative traces from electrophysiological recordings showing the current response to fast application of 10 mM
d
-serine to outside-out membrane patches from HEK-293 cells transfected with GluRδ2 (Upper), GluRδ2Lc (Lower Left), and GluR1 (Lower Right). (Calibration bars: Upper Left, 10 pA, 10 s; Upper Right, 10 pA, 5 ms; Lower Left, 10 pA, 10 s; Lower Right, 50 pA, 5 ms.)
d
-serine did not elicit a current response from WT GluRδ2. For comparison, Lower Right depicts the current–response from the rapidly desensitizing AMPA receptor GluR1 to fast application of 10 mM
l
-glutamate shown on the same timescale as WT GluRδ2. The dashed line indicates the average baseline current, as measured by complete NASP inhibition of the spontaneously activated GluRδ2Lc current. Upon application of
d
-serine to GluRδ2Lc, the current is inhibited to a level corresponding to ≈81% of the NASP inhibition. (D) (Lower) The effect of 1 mM
d
-serine (■) or 50 μM NASP (●) on the constitutive whole-cell current (○) at different membrane potentials in HEK-293 cells expressing GluRδ2Lc. (Upper) Current–voltage relationship was generated by ramping the holding voltage from +45 mV to −50 mV (50 ms) with 10 μM spermine present in the recording pipette, and normalization was performed corresponding to the maximal observed current. (Calibration bar: 100 pA, 50 ms.)